Magnetic retraction: A viable method for the purification of encapsulated islet grafts

Islet cell transplantation is a promising option for the restoration of normal glucose homeostatsis in patients with type-1 diabetes. But problems remain regarding the efficient use of donor cells and the prevention of graft rejection by the host immune system. Previously, we were able to show that xenotransplantation of microencapsulated rat and human islets cells can achieve life-long graft function in immunocompetent diabetic mice without the need for immunosuppression [1]. Since the microencapsulation of islets results in a significant amount of empty capsules, and since graft volume is a crucial issue, we developed a new method which uses magnetic labeling and separation of the microencapsulated islets witch supramagnetic iron particles (SPIO) in order to eliminate empty capsules. For this purpose, rat islets were isolated and labeled with two different concentrations of SPIO (3 and 30µl/ml Resovist®, respectively) before microencapsulation in alginate beads as described [1]. Before transplantation into diabetic mice, the magnetic capsules were separated from the empty capsules using a newly developed linear magnetic flow apparatus. Using this method we were able to reduce the ratio of empty capsules (EC) to islet containing capsules (IC) from 4:1 to at least 2:1 or 1:1 in the low (3µg/ml) and high (30µg/ml) SPIO concentration group, respectively. In vitro viability and functionality assessment using the insulin stimulation index did not show any differences between SPIO-labeted islets and freshly isolated unlabeled islets. For proof of in vivo function 3500 islet equivalents (Ieq) of SPIO-labeled islets from both concentrations were transplanted in the peritoneal cavity of streptozotozin-diabetic immunocompetent balb/c mice, resulting in long term (>30 weeks) normoglycemia. We conclude, that magnetic separation of SPIO-labelled encapsulated islets is a clinically safe and effective principle to significantly decrease the graft volume without impairing graft quality and function